Venom allergen-like protein diversification in flatworms

Abstract

Flatworm Venom Allergen-like Proteins (VAPs) modulate mammalian and avian host immune responses, but their evolutionary origins and functions within symbioses (especially parasitism) remain poorly studied. Previous studies suggest Group 1 VAPs in particular play important roles in host-parasite interactions. These studies have historically focused on taxa of medical and economic value, which represent a small number of the more than 22,000 nominal parasitic flatworm species. The extent to which this observation holds against increased taxonomic sampling remains unknown. To address this gap in taxonomic sampling and better understand the diversification of VAPs across flatworm diversity, we mined new transcriptome assemblies from 21 previously unsampled blood fluke species infecting 19 non-mammalian vertebrate host species, in addition to 26 flatworm transcriptomes and genomes available from public databases. We predicted (1) VAPs would be expressed across flatworm diversity; (2) Group 1, unlike Group 2, VAPs would contain signal peptides consistent with roles in host-parasite interactions; and (3) Group 1 VAPs would exhibit faster rates of amino acid substitutions than Group 2 VAPs. Our bioinformatics approach identified 474 novel VAPs expressed in 45 of 47 flatworm species, including 273 Group 1 VAPs (185 with predicted signal peptides) and 201 Group 2 VAPs (only 2 with predicted signal peptides). We also found evidence of accelerated molecular evolution in Group 1 VAPs. This study is of medical relevance as it is a necessary first step to elucidating VAP members and specific VAP residues that mediate host-specificity and pathogenicity in blood flukes. Moreover, understanding the evolution of gene families involved in flatworm-vertebrate host interactions is important for understanding the genomic bases of parasitism.